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Development of novel antibacterial agents against vancomycin‐resistant bacteria
Author(s) -
Tanksale Aparna,
Pirrung Michael
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a899
Subject(s) - vancomycin , antibiotics , bacteria , chemistry , staphylococcus aureus , microbiology and biotechnology , ic50 , antibiotic resistance , minimum inhibitory concentration , antibacterial activity , vancomycin resistant enterococci , enzyme , biochemistry , biology , in vitro , genetics
Vancomycin is an important, one of the last resort antibiotics used for the treatment of infections by Gram‐positive bacteria such as Staphylococci, Enterococci and Streptococci. The development of bacterial resistance towards such a valuable antibiotic represents an increasing threat to public health. VanS is a histidine kinase and a part of two‐component signal transduction system responsible for signaling resistance to vancomycin in vancomycin‐resistant Enterococci (VRE). It therefore becomes an important target for developing novel antibacterial agents against VRE. Coupled Na + , K + ATPase assay was standardized for the detection of activity of the fusion protein, MBP‐VanS. This assay was then used for the screening of inhibitors. Over 150 compounds were screened for inhibition of MBP‐VanS and their IC 50 values were determined. Out of these, 15 compounds with IC 50 values below 8μM were chosen for determination of the Hill Coefficient, which is an indicator of the number of inhibitor molecules binding to the enzyme. Compounds with good Hill coefficient were selected for determination of their dissociation constant (K i ) and other kinetic parameters, which will lead to the development of better antibacterial agents against VRE. Department of Chemistry, Duke University, Durham, NC, 27708.